Rearrangement of p-Hydroxyphenacyl Esters
treated dropwise with Et N (17.2 mL, 123 mmol) over 15 min and
J. Am. Chem. Soc., Vol. 121, No. 24, 1999 5631
(MeOH) to give 13 (0.96 g, 79%), mp 103-105 °C (lit.24 mp 103-
105 °C).
2-(3,5-Di-tert-butyl-4-hydroxyphenyl)-2-oxoethyl 2-Phenylethan-
oate (14). Compound 14 was prepared as for 13 and the crude product
3
then refluxed for 3 h. The reaction mixture was diluted with ether and
washed with aqueous HCl, water, and brine, dried, and evaporated.
Crystallization from H
33 °C).
O gave 9 (5.7 g, 50%), mp 133 °C (lit.20 mp
2
1
flash chromatographed [EtOAc-hexanes (14:86)] and crystallized
1
(
EtOAc-hexanes) to afford a 58% yield: mp 63-63.5 °C; H NMR
2
-(4-Hydroxyphenyl)-2-oxoethanol (7). A solution of 9 (1.5 g, 7.7
δ (90 MHz, CDCl
1H, s), 7.31 (5H, s), 7.75 (2H, s). Calcd for C24 : C, 75.36; H,
3
) 1.43 (18H, s), 3.80 (2H, s), 5.30 (2H, s), 5.75
mmol) in MeOH (33 mL) and 0.5 M aqueous NaOH (33 mL) was
stirred at room temperature for 15 min and then acidified with aqueous
HCl, and most of the MeOH was evaporated. The residue was extracted
(
7
30 4
H O
.91. Found: C, 75.64; H, 8.01.
-(3,5-Di-tert-butyl-4-hydroxyphenyl)-2-oxoethyl 2,2-Dimethyl-
2
with EtOAc, and the organic phase was washed with H
2
O and brine,
O to give 7
0.79 g, 67%), mp 173 °C (lit. mp 170-172 °C). Under these
conditions there was no evidence of a high-melting product as described
propanoate (15). Compound 15 was prepared as for 13 and the crude
product flash chromatographed [EtOAc-hexanes (7:93)] and crystal-
dried, and evaporated. The residue crystallized from H
2
2
1
(
1
lized (EtOAc-hexanes) to afford a 70% yield: mp 134-135.5 °C; H
2
1
NMR δ (90 MHz, CDCl
.76 (1H, s), 7.78 (2H, s). Calcd for C21
Found: C, 72.16; H, 9.40.
-(3,5-Di-tert-butyl-4-hydroxyphenyl)-2-oxoethyl 2,2-Diphenyl-
-hydroxyacetate (16). Compound 16 was prepared as for 13 and
crystallized (EtOAc-hexanes) to afford a 69% yield: mp 151-152
3
) 1.30 (9H, s), 1.45 (18H, s), 5.29 (2H, s),
previously.
-(4-Hydroxyphenyl)-2-oxoethyl Phenylacetate (10). Compound
0 was prepared as described for 9, purified by flash chromatography
EtOAc-hexanes (2:3)], and crystallized (EtOAc-hexanes): mp 106-
5
32 4
H O
: C, 72.38; H, 9.26.
2
1
2
[
2
1
1
5
9
5
07 °C; H NMR δ [90 MHz; CDCl
.30 (2H, s), 6.82 (2H, d, J ) 9 Hz), 7.31 (5H, s), 7.77 (2H, d, J
: C, 71.10; H, 5.22. Found: C, 70.92, H,
3
3
-CD OD (9:1)] 3.80 (2H, s),
o
o
)
1
°
(
C; H NMR δ (90 MHz, CDCl
2H, s), 5.80 (1H, s), 7.24-7.68 (10H, m), 7.76 (2H, s). Calcd for
: C, 75.92; H, 7.22. Found: C, 75.84; H, 7.23.
Product Studies. Preparative photolyses were carried out with
3
) 1.45 (18H, s), 4.16 (1H, br s), 5.43
Hz). Calcd for C16
14 4
H O
.21.
30 34 5
C H O
2
-(4-Hydroxyphenyl)-2-oxoethyl 2,2-Dimethylpropanoate (11):
1
mp 178.5 °C (EtOAc-hexanes); H NMR δ [90 MHz; CDCl
9:1)] 1.29 (9H, s), 5.25 (2H, s), 6.84 (2H, d, J ) 9 Hz), 7.78 (2H, d,
) 9 Hz). Calcd for C13 : C, 66.08; H, 6.82. Found: C, 65.75;
H, 6.78.
3 3
-CD OD
samples (20-100 mg) dissolved in the appropriate solvent (40-100
mL) and transferred to a quartz tube. The solution was irradiated at
300 nm with continuous cooling (by a coldfinger) and purging by a
stream of argon for approximately 15 min before and continuously
during irradiation (via a long stainless steel needle). Photolysis times
ranged from 3 to 30 min, depending on the conversion desired, the
efficiency of the reaction, and the size of the sample. After photolysis,
aqueous samples were worked up by extraction with CH Cl after
2 2
addition of NaCl. Direct evaporation of the organic solvent was used
when samples were irradiated in wholly organic solvents.
(
J
o
o
16 4
H O
2-(4-Hydroxyphenyl)-2-oxoethyl 2,2-Diphenyl-2-hydroxyacetate
(12). Aqueous NaOH (1 M) was added to a suspension of benzilic
acid (2.28 g, 10 mmol) in water (10 mL) to adjust the pH to 6.7.
p-Hydroxyphenacyl chloride (0.85 g, 5.0 mmol) and sodium iodide
(0.15 g, 1.0 mmol) were added, and the mixture was refluxed for 3.5
h. The cooled mixture was extracted with ether, and the organic extract
was washed with water, 250 mM pH 5.5 NaOAc buffer, and brine,
dried, and evaporated. Flash chromatography [EtOAc-hexanes (2:3)]
Analytical photolysis runs were carried out by direct photolysis of
samples in NMR tubes. A solution was made by dissolving 2-3 mg
of substrate in ∼2 mL of 1:1 D
2
3
O-CD CN. The solution was then
gave 12 as an amorphous solid (from hexanes) (0.69 g, 38%): mp
1
purged by argon for 10 min, and transferred to an NMR tube. This
NMR tube was subsequently placed in the middle of a Rayonet RPR
100 photochemical reactor and irradiated at 300 nm. An internal fan
in the reactor was used to cool the sample during the photolysis.
Photolysis times ranged from 1 to 10 min, depending on the number
of lamps used, the conversion desired, the efficiency of the reaction,
1
55-156 °C; H NMR δ [90 MHz; CDCl
3
-CD
) 9 Hz), 7.19-7.66 (10H, m), 7.77
) 9 Hz); FAB-MS, m/e (M + Na)+ calcd for C22
Na 385.1040, found 385.1052.
3
OD (9:1)] 2.88 (1H,
s), 5.39 (2H, s), 6.82 (2H, d, J
2H, d, J
o
(
o
18 5
H O +
2
-Bromo-1-(3,5-di-tert-butyl-4-hydroxyphenyl)ethanone. This com-
22
pound was obtained by a modified procedure of Karhunen et al.
A
1
and the size of the sample. H NMR spectra were taken directly after
solution of 1-(3,5-di-tert-butyl-4-hydroxyphenyl)ethanone23 (10.0 g,
the photolysis without further treatment. Typical experiments are
described below.
4
5
0.32 mmol) in EtOH (350 mL) was treated with bromine (2.6 mL,
0.4 mmol) in one portion, and nitrogen was bubbled continuously
Photolysis of 9 in 1:1 H
2
O-CH
3
CN. Compound 9 (20 mg) was
into the stirred mixture. After 30 min the nitrogen flow and stirring
rate were both increased. After a further 2 h the solution was
concentrated to ∼50 mL and kept overnight at 4 °C. The title bromide
dissolved in 1:1 H O-CH CN (40 mL), and the solution was irradiated
2
3
for 3 min by eight lamps using the procedure for preparative photolysis.
1
After workup and evaporation of the solvent, H NMR of the
(
9.56 g, 73%) was filtered and dried: mp 107.5-108.5 °C (from
photolyzate showed that conversion to photoproduct 3 was 40% (the
remaining was starting material 9). Separation by preparative TLC
1
hexanes); H NMR δ (90 MHz; CDCl
.82 (1H, s), 7.87 (2H, s). Calcd for C16
Found: C, 58.48; H, 6.98.
3
) 1.44 (18H, s), 4.37 (2H, s),
5
H23BrO
2
: C, 58.72; H, 7.08.
(
silica, 10:1 CH
2 2
Cl -EtOAc) gave the pure photoproduct, p-hydroxy-
phenylacetic acid (3). Conversion was 90-95% when a sample was
photolyzed for 10 min. H NMR δ ((CD ) CO) 3.48 (2H, s), 6.76 (2H,
3 2
1
2
-(3,5-Di-tert-butyl-4-hydroxyphenyl)-2-oxoethyl Acetate (13). On
3
b
25
the basis of the method of Park and Givens, a solution of 2-bromo-
-(3,5-di-tert-butyl-4-hydroxyphenyl)ethanone (1.31 g, 4.0 mmol) and
d, J ) 9 Hz), 7.10 (2H, d, J ) 9 Hz); mp 148-150 °C (lit. mp 149-
+
1
151 °C); MS (CI) m/z 153 (M + 1). Compound 9 was also studied
glacial HOAc (0.3 mL, 5.2 mmol) in dry toluene (52 mL) was cooled
to 0 °C, and DBU (0.78 mL, 5.2 mmol) was added in one portion. The
solution was stirred in ice for 1 h and then overnight at room
by the procedure for analytical runs, as for 10-12 (see below).
3
Photolysis of 9 in CH OH. Using the procedure for preparative
photolyses, solutions of 9 (20 mg) dissolved in neat CH
3
OH (40 mL)
temperature and diluted with Et
2
O. The solution was washed with H
2
O
were irradiated by eight lamps for 15 min. Conversion to methyl
and brine, dried, and evaporated, and the residue was crystallized
p-hydroxyphenylacetate was 40%, which was separated by preparative
TLC (silica, 2:1 hexanes-EtOAc): 1H NMR δ ((CD
)
3
2
CO) 3.48 (2H,
s), 3.61 (3H, s), 6.0 (1H, s, exchangeable with D
2
O), 6.76 (2H, d, J )
(
18) Alexander, J.; Renyer, M. L.; Veerapanane, H. Synth. Commun.
995, 25, 3875.
19) Winterhalder, L. US Patent 2 838 570; Chem. Abstr. 1958, 52,
6301.
9
Hz), 7.10 (2H, d, J ) 9 Hz); this spectrum is identical to that reported
25 25
1
(
for the authentic sample; mp 55-56 °C (lit. mp 59 °C); MS (CI)
+
1
m/z 167 (M + 1).
(
(
(
20) Robertson, A.; Robinson, R. J. Chem. Soc. 1928, 1460.
21) Tedder, J. M.; Theaker, G. J. Chem. Soc. 1959, 257.
22) Karhunen, P.; Rummakko, P.; Pajunen, A.; Brunow, G. J. Chem.
(24) Engelhardt, M.; Fruhstorfer, W.; Hesse, R.; Dennler, B.; Baumer,
W. German Patent 1 811 322; Chem. Abstr. 1970, 73, 55826.
(25) Pouchert, C. J.; Behnke, J. The Aldrich Library of 1 C and H FT
NMR Spectra, Edition I; Aldrich Chemical Co.: Milwaukee, WI, 1993;
Vol. 2.
3
1
Soc., Perkin Trans. 1 1996, 2303.
23) Matsuura, T.; Nishinaga, A.; Cahnmann, H. J. J. Org. Chem. 1962,
7, 3620.
(
2